The present invention generally relates to drug delivery and electrical stimulation systems and methods, and more particularly relates to utilizing one or more devices to deliver electrical stimulation and/or one or more stimulating drugs for the modulation of pancreatic endocrine secretion and as a treatment for diabetes.
Twelve to fifteen million people in the United States suffer from diabetes mellitus (which is often, as herein, simply referred to as diabetes). Diabetes is a syndrome characterized by disordered metabolism and inappropriately high levels of blood glucose, i.e., hyperglycemia. Diabetes is classified into two distinct types. Type 1, also known as Insulin-Dependent Diabetes Mellitus (IDDM), is believed to be due to autoimmune destruction of beta cells in the pancreas, which are the only cells in the body that produce and secrete insulin. Type 1 occurs most commonly in juveniles but occasionally in adults. Type 2, also known as Non-Insulin-Dependent Diabetes Mellitus (NIDDM), is a milder form of diabetes that usually occurs in adults.
Up to about 10% of people with diabetes have type 1 diabetes, and are dependent on daily exogenous insulin. Insulin, a small protein, is degraded when taken orally; thus, it must be administered parenterally. Thus, most patients take insulin through injection. An increasing number are receiving insulin through a percutaneous pump, but this requires external apparatus that must be worn continuously. A fully implantable pump is also available, requiring monthly visits to a physician to refill the pump. An inhaled version of insulin is under development. Additional treatment options are needed.
The invention disclosed and claimed herein provides modulation of pancreatic endocrine secretion and treatment or prevention of diabetes, via one or a combination of systems and methods. Some systems and methods of the present invention provide electrical stimulation of pancreatic cells, and particularly of alpha and delta cells, as well as beta cells. Stimulation to depolarize/hyperpolarize alpha and delta cells modulates the secretion of glucagon and somatostatin, respectively, which in turn affects the secretion of insulin by beta cells. In addition, the present invention teaches hyperpolarization of pancreatic beta cells, for inhibiting the secretion of insulin during periods of hypoglycemia. Further, the present invention teaches effective frequencies for electrical stimulation, so that stimulation of pancreatic islet cells is maximized while the stimulation of other structures is minimized.
Additional systems and methods taught herein provide electrical stimulation of autonomic nerves and/or ganglia innervating the pancreas, thereby modulating insulin and glucagon secretion. For example, stimulation to decrease the excitement of sympathetic input to the pancreatic beta cells will increase insulin production.
Other systems and methods of the present invention provide the application of a stimulating drug(s) alone or in combination with electrical stimulation. These drugs may modulate the release of insulin, somatostatin, and glucagon. This invention also includes the possibility of combining stimulation with medication released from an implanted reservoir (i.e., a drug pump).
Electrical and/or drug stimulation of specific sites innervating and/or within the pancreas, and the resulting changes in secretion of insulin, glucagon, and somatostatin, may have significant therapeutic benefit in the control of diabetes. In addition, it is believed that 1) insulin and somatostatin secretions induced by glucose are inhibited during SNS through alpha-adrenergic activation, 2) insulin and somatostatin secretions are stimulated during SNS through beta-adrenergic activation, and 3) SNS-induced glucagon secretion occurs mainly through alpha-adrenergic activation.
This invention may prove beneficial in cases of transplanted beta cells, wherein the cells have no innervation lo modulate insulin secretion. This invention may also prove beneficial in cases of blunted or absent response of endogenous pancreatic endocrine tissue to neural stimulation. Additional potential (but not necessary) uses of the present invention include, but are not limited to, application to diabetes prevention, e.g., by inhibiting glucagon and/or somatostatin from attenuating the effects of insulin, possibly by decreasing glucagon and/or somatostatin plasma levels.
The invention is carried out via one or more system control units (SCUs) that apply electrical stimulation and/or one or more stimulating drugs to one or more predetermined stimulation sites. In some forms of SCUs, one or more electrodes are surgically implanted to provide electrical stimulation from an implantable signal/pulse generator (IPG) and/or one or more infusion outlets and/or catheters are surgically implanted to infuse drug(s) from an implantable pump. When necessary and/or desired, an SCU provides both electrical stimulation and one or more stimulating drugs. In other forms of an SCU, a miniature implantable neurostimulator (a.k.a., a microstimulator), such as a Bionic Neuron (also referred to as a BION(copyright) microstimulator), is implanted. Some forms of the disclosed systems also include one or more sensors for sensing symptoms or other conditions that may indicate a needed treatment.
The SCU may include a programmable memory for storing data and/or control parameters. This allows stimulation and control parameters to be adjusted to levels that are safe and efficacious with minimal discomfort. Electrical and drug stimulation may be controlled independently; alternatively, electrical and drug stimulation may be coupled, e.g., electrical stimulation may be programmed to occur only during drug infusion.
According to some embodiments of the invention, the electrodes used for electrical stimulation are arranged as an array on a thin implantable lead. The SCU may be programmed to produce either monopolar electrical stimulation, e.g., using the SCU case as an indifferent electrode, or bipolar electrical stimulation, e.g., using one of the electrodes of the electrode array as an indifferent electrode. The SCU may include a means of stimulating tissue or infusing a stimulating drug(s) either intermittently or continuously. Specific stimulation/infusion parameters may provide therapy for, e.g., varying types and degrees of severity of diabetes.
The SCU used with the present invention possesses one or more of the following properties, among other properties:
at least two electrodes for applying stimulating current to surrounding tissue and/or a pump and at least one outlet for delivering a drug or drugs to surrounding tissue;
electronic and/or mechanical components encapsulated in a hermetic package made from biocompatible material(s);
an electrical coil inside the package that receives power and/or data by inductive or radio-frequency (RF) coupling to a transmitting coil placed outside the body, avoiding the need for electrical leads to connect devices to a central implanted or external controller;
means for receiving and/or transmitting signals via telemetry;
means for receiving and/or storing electrical power within the SCU; and
a form factor making the SCU implantable in a target area in the body.
The power source of the SCU is realized using one or more of the following options, or the like:
(1) an external power source coupled to the SCU via a radio-frequency (RF) link;
(2) a self-contained power source made using any means of generation or storage of energy, e.g., a primary battery, a replenishable or rechargeable battery, a capacitor, a supercapacitor; and/or
(3) if the self-contained power source is replenishable or rechargeable, a means of replenishing or recharging the power source, e.g., an RF link, an optical link, or other energy-coupling link.
According to certain embodiments of the invention, an SCU operates independently. According to various embodiments of the invention, an SCU operates in a coordinated manner with other implanted SCUs, other implanted devices, or with devices external to the patient""s body.
According to several embodiments of the invention, an SCU incorporates means of sensing the disorder or symptoms thereof, or other measures of the state of the patient. Sensed information may be used to control the electrical and/or drug stimulation parameters of the SCU in a closed loop manner. According to some embodiments of the invention, the sensing and stimulating means are incorporated into a single SCU. According to several embodiments of the invention, the sensing means communicates sensed information to at least one SCU with stimulating means.